RANGAP1

RANGAP1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1Z5S, 2GRN, 2GRO, 2GRP, 2GRQ, 2GRR, 2IY0, 3UIN, 3UIO, 3UIP, 5D2M, 2IO2, 2IO3
Identifiers
Aliases	RANGAP1 , Fug1, RANGAP, SD, Ran GTPase activating protein 1
External IDs	OMIM: 602362; MGI: 103071; HomoloGene: 55700; GeneCards: RANGAP1; OMA:RANGAP1 - orthologs
Gene location (Human) Chr. Chromosome 22 (human) [1] Band 22q13.2 Start 41,244,779 bp [1] End 41,286,187 bp [1]
Gene location (Mouse) Chr. Chromosome 15 (mouse) [2] Band 15 E1|15 38.21 cM Start 81,588,449 bp [2] End 81,629,731 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in left testis right testis Brodmann area 10 right frontal lobe cingulate gyrus anterior cingulate cortex skin of abdomen Brodmann area 9 skin of leg middle frontal gyrus Top expressed in dentate gyrus of hippocampal formation granule cell superior surface of tongue spermatid yolk sac visual cortex superior frontal gyrus seminiferous tubule gallbladder primary visual cortex epiblast More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding cadherin binding RNA binding GTPase activator activity ubiquitin protein ligase binding Cellular component intracellular membrane-bounded organelle cytoplasmic periphery of the nuclear pore complex nuclear pore chromosome dendrite nuclear pore cytoplasmic filaments mitotic spindle chromosome, centromeric region cytoskeleton nucleus kinetochore axon cytoplasm cytoplasm cytosol aggresome perinuclear region of cytoplasm nuclear envelope nucleoplasm spindle nuclear membrane Biological process cellular response to vasopressin protein sumoylation cellular response to peptide hormone stimulus negative regulation of protein export from nucleus response to axon injury signal transduction sister chromatid cohesion activation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5905 19387 Ensembl ENSG00000100401 ENSMUSG00000022391 UniProt P46060 P46061 RefSeq (mRNA) NM_001278651 NM_002883 NM_001317930 NM_001146174 NM_011241 NM_001358622 RefSeq (protein) NP_001265580 NP_001304859 NP_002874 NP_001139646 NP_035371 NP_001345551 Location (UCSC) Chr 22: 41.24 – 41.29 Mb Chr 15: 81.59 – 81.63 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Further informationon RanGAP proteins in non-human species: RanGAP

Ran GTPase-activating protein 1 is an enzyme that in humans is encoded by the RANGAP1 gene. ^{[5] [6]}

Function

RanGAP1, is a homodimeric 65-kD polypeptide that specifically induces the GTPase activity of RAN, but not of RAS by over 1,000-fold. RanGAP1 is the immediate antagonist of RCC1, a regulator molecule that keeps RAN in the active, GTP-bound state. The RANGAP1 gene encodes a 587-amino acid polypeptide. The sequence is unrelated to that of GTPase activators for other RAS-related proteins, but is 88% identical to Rangap1 (Fug1), the murine homolog of yeast Rna1p. RanGAP1 and RCC1 control RAN-dependent transport between the nucleus and cytoplasm. RanGAP1 is a key regulator of the RAN GTP/GDP cycle. ^[6]

Interactions

RanGAP1 is a trafficking protein which helps transport other proteins from the cytoplasm to the nucleus. Small ubiquitin-related modifier needs to be associated with it before it can be localized at the nuclear pore. ^[7]

RANGAP1 has been shown to interact with:

• Ran, ^{[8] [9] [10]} and
• UBE2I. ^{[11] [12] [13]}

References

1. GRCh38: Ensembl release 89: ENSG00000100401 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000022391 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bischoff FR, Krebber H, Kempf T, Hermes I, Ponstingl H (Apr 1995). "Human RanGTPase-activating protein RanGAP1 is a homologue of yeast Rna1p involved in mRNA processing and transport". Proc Natl Acad Sci U S A. 92 (5): 1749–53. Bibcode:1995PNAS...92.1749B. doi: 10.1073/pnas.92.5.1749 . PMC   42597 . PMID   7878053.
6. "Entrez Gene: RANGAP1 Ran GTPase activating protein 1".
7. Hochstrasser M (2000). "Biochemistry. All in the ubiquitin family". Science. 289 (5479): 563–4. doi:10.1126/science.289.5479.563. PMID   10939967. S2CID   32469429.
8. Hillig RC, Renault L, Vetter IR, Drell T, Wittinghofer A, Becker J (Jun 1999). "The crystal structure of rna1p: a new fold for a GTPase-activating protein". Mol. Cell. 3 (6): 781–91. doi: 10.1016/S1097-2765(01)80010-1 . PMID   10394366.
9. Becker J, Melchior F, Gerke V, Bischoff FR, Ponstingl H, Wittinghofer A (May 1995). "RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae". J. Biol. Chem. 270 (20): 11860–5. doi: 10.1074/jbc.270.20.11860 . PMID   7744835.
10. Bischoff FR, Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H (Mar 1994). "RanGAP1 induces GTPase activity of nuclear Ras-related Ran". Proc. Natl. Acad. Sci. U.S.A. 91 (7): 2587–91. Bibcode:1994PNAS...91.2587B. doi: 10.1073/pnas.91.7.2587 . PMC   43414 . PMID   8146159.
11. Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, McBroom-Cerajewski L, Robinson MD, O'Connor L, Li M, Taylor R, Dharsee M, Ho Y, Heilbut A, Moore L, Zhang S, Ornatsky O, Bukhman YV, Ethier M, Sheng Y, Vasilescu J, Abu-Farha M, Lambert JP, Duewel HS, Stewart II, Kuehl B, Hogue K, Colwill K, Gladwish K, Muskat B, Kinach R, Adams SL, Moran MF, Morin GB, Topaloglou T, Figeys D (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3: 89. doi:10.1038/msb4100134. PMC   1847948 . PMID   17353931.
12. Tatham MH, Kim S, Yu B, Jaffray E, Song J, Zheng J, Rodriguez MS, Hay RT, Chen Y (Aug 2003). "Role of an N-terminal site of Ubc9 in SUMO-1, -2, and -3 binding and conjugation". Biochemistry. 42 (33): 9959–69. doi:10.1021/bi0345283. PMID   12924945.
13. Knipscheer P, Flotho A, Klug H, Olsen JV, van Dijk WJ, Fish A, Johnson ES, Mann M, Sixma TK, Pichler A (Aug 2008). "Ubc9 sumoylation regulates SUMO target discrimination". Mol. Cell. 31 (3): 371–82. doi: 10.1016/j.molcel.2008.05.022 . PMID   18691969.

Further reading

• Becker J, Melchior F, Gerke V, Bischoff FR, Ponstingl H, Wittinghofer A (1995). "RNA1 encodes a GTPase-activating protein specific for Gsp1p, the Ran/TC4 homologue of Saccharomyces cerevisiae". J. Biol. Chem. 270 (20): 11860–5. doi: 10.1074/jbc.270.20.11860 . PMID   7744835.
• Bischoff FR, Klebe C, Kretschmer J, Wittinghofer A, Ponstingl H (1994). "RanGAP1 induces GTPase activity of nuclear Ras-related Ran". Proc. Natl. Acad. Sci. U.S.A. 91 (7): 2587–91. Bibcode:1994PNAS...91.2587B. doi: 10.1073/pnas.91.7.2587 . PMC   43414 . PMID   8146159.
• Krebber H, Ponstingl H (1997). "Ubiquitous expression and testis-specific alternative polyadenylation of mRNA for the human Ran GTPase activator RanGAP1". Gene. 180 (1–2): 7–11. doi:10.1016/S0378-1119(96)00389-7. PMID   8973340.
• Matunis MJ, Coutavas E, Blobel G (1997). "A novel ubiquitin-like modification modulates the partitioning of the Ran-GTPase-activating protein RanGAP1 between the cytosol and the nuclear pore complex". J. Cell Biol. 135 (6 Pt 1): 1457–70. doi:10.1083/jcb.135.6.1457. PMC   2133973 . PMID   8978815.
• Mahajan R, Delphin C, Guan T, Gerace L, Melchior F (1997). "A small ubiquitin-related polypeptide involved in targeting RanGAP1 to nuclear pore complex protein RanBP2". Cell. 88 (1): 97–107. doi: 10.1016/S0092-8674(00)81862-0 . PMID   9019411.
• Görlich D, Dabrowski M, Bischoff FR, Kutay U, Bork P, Hartmann E, Prehn S, Izaurralde E (1997). "A Novel Class of RanGTP Binding Proteins". J. Cell Biol. 138 (1): 65–80. doi:10.1083/jcb.138.1.65. PMC   2139951 . PMID   9214382.
• Scheffzek K, Ahmadian MR, Kabsch W, Wiesmüller L, Lautwein A, Schmitz F, Wittinghofer A (1998). "The Ras-RasGAP complex: structural basis for GTPase activation and its loss in oncogenic Ras mutants". Science. 277 (5324): 333–8. doi:10.1126/science.277.5324.333. PMID   9219684.
• Mahajan R, Gerace L, Melchior F (1998). "Molecular Characterization of the SUMO-1 Modification of RanGAP1 and Its Role in Nuclear Envelope Association". J. Cell Biol. 140 (2): 259–70. doi:10.1083/jcb.140.2.259. PMC   2132567 . PMID   9442102.
• Kamitani T, Kito K, Nguyen HP, Fukuda-Kamitani T, Yeh ET (1998). "Characterization of a second member of the sentrin family of ubiquitin-like proteins". J. Biol. Chem. 273 (18): 11349–53. doi: 10.1074/jbc.273.18.11349 . PMID   9556629.
• Okuma T, Honda R, Ichikawa G, Tsumagari N, Yasuda H (1999). "In vitro SUMO-1 modification requires two enzymatic steps, E1 and E2". Biochem. Biophys. Res. Commun. 254 (3): 693–8. doi:10.1006/bbrc.1998.9995. PMID   9920803.
• Hillig RC, Renault L, Vetter IR, Drell T, Wittinghofer A, Becker J (1999). "The crystal structure of rna1p: a new fold for a GTPase-activating protein". Mol. Cell. 3 (6): 781–91. doi: 10.1016/S1097-2765(01)80010-1 . PMID   10394366.
• Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi: 10.1038/990031 . PMID   10591208.
• Nagase T, Nakayama M, Nakajima D, Kikuno R, Ohara O (2001). "Prediction of the coding sequences of unidentified human genes. XX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 8 (2): 85–95. doi: 10.1093/dnares/8.2.85 . PMID   11347906.
• Bernier-Villamor V, Sampson DA, Matunis MJ, Lima CD (2002). "Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1". Cell. 108 (3): 345–56. doi: 10.1016/S0092-8674(02)00630-X . PMID   11853669.
• Joseph J, Tan SH, Karpova TS, McNally JG, Dasso M (2002). "SUMO-1 targets RanGAP1 to kinetochores and mitotic spindles". J. Cell Biol. 156 (4): 595–602. doi:10.1083/jcb.200110109. PMC   2174074 . PMID   11854305.
• Zhang H, Saitoh H, Matunis MJ (2002). "Enzymes of the SUMO Modification Pathway Localize to Filaments of the Nuclear Pore Complex". Mol. Cell. Biol. 22 (18): 6498–508. doi:10.1128/MCB.22.18.6498-6508.2002. PMC   135644 . PMID   12192048.
• Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proc. Natl. Acad. Sci. U.S.A. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi: 10.1073/pnas.0404720101 . PMC   514446 . PMID   15302935.
• Macauley MS, Errington WJ, Okon M, Schärpf M, Mackereth CD, Schulman BA, McIntosh LP (2005). "Structural and dynamic independence of isopeptide-linked RanGAP1 and SUMO-1". J. Biol. Chem. 279 (47): 49131–7. doi: 10.1074/jbc.M408705200 . PMID   15355965.